Sirolimus, tacrolimus and low-dose methotrexate based graft-versus-host disease prophylaxis after non-ablative or reduced intensity conditioning in related and unrelated donor allogeneic hematopoietic cell transplant

Abstract

Encouraging results have been reported with sirolimus, tacrolimus and low-dose methotrexate after non-myeloablative allogeneic hematopoietic cell transplant. We conducted a retrospective analysis of 71 patients with lymphoid malignancies treated with this prophylaxis regimen after non-myeloablative or reduced intensity allogeneic hematopoietic cell transplant. Grafts were human leukocyte antigen (HLA)-matched related in 29 (41%), matched unrelated in 36 (51%) and 9/10 HLA-matched unrelated in six (8%) patients. The regimen was well tolerated and over 90% of patients completed the planned treatment. The cumulative incidences of 1-year grade B–D and C–D acute graft-versus-host disease (GVHD) were 0.28 (95% confidence interval [CI], 0.18–0.39) and 0.07 (95% CI, 0.03–0.15), respectively, and of 1- and 2-year chronic GVHD (National Institutes of Health criteria) in 70 evaluable patients were 0.15 (95% CI, 0.08–0.24) and 0.33 (95% CI, 0.22–0.44), respectively. The median day of onset of acute GVHD was 123 days (range, 17–268 days). Peri-transplant rituximab or anti-thymocyte globulin did not affect GVHD. The cumulative incidence of 1-year non-relapse mortality and relapse were 4% and 20%, respectively. With a median follow-up of 3.5 (range: 0.18–5.1) years, overall survival and progression-free survival at 2 years were 82% and 66%, respectively. This GVHD regimen results in a low incidence and severity of acute and chronic GVHD after reduced intensity and non-myeloablative allogeneic hematopoietic cell transplant for lymphoid malignancies. The study also highlights the incidence of late onset acute GVHD in non-myeloablative/reduced intensity conditioning, and the contribution of the new GVHD staging system that more accurately reflects clinical outcomes.

Keywords::

• Sirolimus
• reduced intensity
• non-myeloablative conditioning
• graft-versus-host disease

Acknowledgements

We gratefully acknowledge the expert care provided to our patients by the fellows, mid-level providers and nurses of Memorial Sloan Kettering Cancer Center.

This work was supported in part by the Programa de Formación Avanzada en Oncología (PAO) 2011 de la Asociación Española contra el Cáncer (AECC) and Ayudas para la Formación Continuada en Ciencias de la Salud del Gobierno de Navarra.

Potential conflict of interest: Disclosure forms provided by the authors are available with the full text of this article at www.informahealthcare.com/lal.